Human Molecular Genetics, Vol 6, 1811-1816, Copyright © 1997 by Oxford University Press
JE Nielsen, P Koefoed, K Abell, L Hasholt, H Eiberg, K Fenger, E Niebuhr and SA Sorensen
CAG repeat expansions have been identified as the disease-causing dynamic
mutations in the coding regions of genes in several dominantly inherited
neurodegenerative disorders, including spinobulbar muscular atrophy,
Huntington's disease, dentatorubral-pallidoluysian atrophy, spinocerebellar
ataxia type 1, 2 and 6 and Machado-Joseph disease. The CAG repeat
expansions are translated to elongated polyglutamine tracts and an
increased size of the polyglutamine tract correlates with anticipation, the
cardinal feature, seen in all these diseases. Autosomal dominant pure
spastic peraplegia (ADPSP) is a degenerative disorder of the central motor
system clinically characterized by slowly progressive and unremitting
spasticity of the legs, hyperreflexia and Babinski's sign. Like the
established CAG repeat diseases ADPSP is characterized by both inter- and
intrafamilial variation and anticipation. Using the Repeat Expansion
Detection (RED) method, we have analyzed 21 affected individuals from six
Danish families with the disease linked to chromosome 2p21-p24. We found
that 20 of 21 affected individuals showed CAG repeat expansions versus two
of 21 healthy spouses, demonstrating a strongly statistically significant
association between the occurrence of the repeat expansion and the disease
(Fisher's test, P < 10(-5)) suggesting that a CAG repeat expansion is
involved presumably as a dynamic mutation in ADPSP linked to chromosome
2p21-p24. The size of the expansion is estimated to be > or = 60 CAG
repeat copies in the affected individuals. The CAG repeat expansion is very
likely translated and expressed as indicated by the detection of a
polyglutamine-containing protein in an ADPSP patient.
ARTICLES
CAG repeat expansion in autosomal dominant pure spastic paraplegia linked to chromosome 2p21-p24
Department of Medical Genetics, Panum Institute, University of Copenhagen, Denmark.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K.A. Freed, D.W. Cooper, S.P. Brennecke, and E.K. Moses Detection of CAG repeats in pre-eclampsia/eclampsia using the repeat expansion detection method Mol. Hum. Reprod., July 1, 2005; 11(7): 481 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Starling, P Rocco, M R Passos-Bueno, J Hazan, S K Marie, and M Zatz Autosomal dominant (AD) pure spastic paraplegia (HSP) linked to locus SPG4 affects almost exclusively males in a large pedigree J. Med. Genet., December 1, 2002; 39(12): e77 - 77. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Hoffner, P. Kahlem, and P. Djian Perinuclear localization of huntingtin as a consequence of its binding to microtubules through an interaction with {beta}-tubulin: relevance to Huntington's disease J. Cell Sci., January 3, 2002; 115(5): 941 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. McMonagle, P.C. Byrne, B. Fitzgerald, S. Webb, N.A. Parfrey, and M. Hutchinson Phenotype of AD-HSP due to mutations in the SPAST gene: Comparison with AD-HSP without mutations Neurology, December 26, 2000; 55(12): 1794 - 1800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. McDermott, K White, K Bushby, and P. Shaw Hereditary spastic paraparesis: a review of new developments J. Neurol. Neurosurg. Psychiatry, August 1, 2000; 69(2): 150 - 160. [Full Text] [PDF]
|
|
|
|
|
|
I Vuillaume, P Meynieu, S Schraen-Maschke, A Destée, and B Sablonnière Absence of unidentified CAG repeat expansion in patients with Huntington's disease-like phenotype J. Neurol. Neurosurg. Psychiatry, May 1, 2000; 68(5): 672 - 675. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. Reid, C. Grayson, M. T. Rogers, and D. C. Rubinsztein Locus–phenotype correlations in autosomal dominant pure hereditary spastic paraplegia: A clinical and molecular genetic study of 28 United Kingdom families Brain, September 1, 1999; 122(9): 1741 - 1755. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Coutinho, J. Barros, R. Zemmouri, J. Guimaraes, C. Alves, R. Chorao, E. Lourenco, P. Ribeiro, J. L. Loureiro, J. V. Santos, et al. Clinical Heterogeneity of Autosomal Recessive Spastic Paraplegias: Analysis of 106 Patients in 46 Families Arch Neurol, August 1, 1999; 56(8): 943 - 949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Figlewicz and T. D. Bird ""Pure"" hereditary spastic paraplegias Neurology, July 1, 1999; 53(1): 5 - 5. [Full Text]
|
|
|
|
|
|
P. Hedera, S. DiMauro, E. Bonilla, J. Wald, O. P. Eldevik, and J. K. Fink Phenotypic analysis of autosomal dominant hereditary spastic paraplegia linked to chromosome 8q Neurology, July 1, 1999; 53(1): 44 - 44. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Martin Molecular Basis of the Neurodegenerative Disorders N. Engl. J. Med., June 24, 1999; 340(25): 1970 - 1980. [Full Text] [PDF]
|
|
|
|
|
|
L N. Jensen, T Gerstenberg, E B Kallestrup, P Koefoed, J Nordling, and J E Nielsen Urodynamic evaluation of patients with autosomal dominant pure spastic paraplegia linked to chromosome 2p21-p24 J. Neurol. Neurosurg. Psychiatry, November 1, 1998; 65(5): 693 - 696. [Abstract] [Full Text]
|
|